The goal of this project is to provide a better understanding of the biochemical processes involved in normal enchondral ossification. Proteoglycan aggregates in epiphyseal cartilage and in the zone of proliferating chondrocytes inhibit mineralization. Proteoglycan aggregates are in some way structurally modified in the zone of hypertrophic chondrocytes so that their capacity to inhibit mineralization is abolished. One major objective of this project is to show how proteoglycan aggregates are structually modified in growth plate so that a non-calcifiable matrix is transformed into a calcifiable matrix. The proposed studies will involve (a) isolation and characterization of proteoglycan species and selected matrix protein species from epiphyseal cartilage and from the different zones of growth plate cartilage; (b) studies of the structures and functions of these species; (c) studies of the assembly of link protein, proteoglycan monomer and hyaluronate into proteoglycan aggregates, and of the capacity of selected matrix protein species to displace link protein and proteoglycan monomers from hyaluronte, dissociate aggregates, and abolish the capacity of the aggregates to inhibit mineralization.